Mesothelioma pulmonary adenocarcinoma

Cytokeratin Profiles of Epithelial Mesothelioma, Pulmonary Adenocarcinoma, and Squamous Cell Carcinoma of Lung ... 

Ryan PJ, Oates JL, Crocker J, et al. 1997. Distinction between pleural mesothelioma and pulmonary adenocarcinoma using MOC31 in an asbestos sprayer. Resp Med 91 57-60. 

Wick MR, Toy T, Mills SE, et al. Malignant epithelioid pleural mesothelioma versus peripheral pulmonary adenocarcinoma A histochemical, ultrastructural, and immunohistologic study of 103 cases. Hum Pathol. 1990 21 759-766. 

Kahn and coworkers reported a difference in the pattern of keratin distribution in benign and malignant mesothelial cells compared to adenocarcinomas. In mesothelial cells, the authors observed keratin filaments in a perinuclear or peripheral distribution, whereas in adenocarcinomas they saw an arborizing pattern. In a more extensive study, 10 adenocarcinomas, 10 typical carcinoids, and 4 mesotheliomas were evaluated for keratin intermediate filament distribution using three monoclonal and three polyclonal antibodies against keratin. When the authors allowed the diaminobenzi-dine color reaction to proceed for less than two minutes, they observed a web-like pattern of reactivity in adenocarcinomas, a punctate crescentic pattern in carcinoids, and a perinuclear-staining pattern in mesotheliomas. While the perinuclear distribution of keratin intermediate filaments is common in epithelial mesotheliomas, it is not seen in all cases, and some pulmonary adenocarcinomas show a perinuclear distribution of keratin. Hence we do not use the distribution pattern of keratin diagnostically. 

Additional studies have shown a high degree of specificity and sensitivity for calretinin in differentiating epithelial mesotheliomas from pulmonary adenocarcinomas and other epithelioid neoplasms. 733... 

The use of the MEl antibody was initially reported by O Hara and colleagues in 1990. " MEl is a monoclonal antibody generated from the mesothelial cell line SPClll and reacted with normal mesothelial cells and malignant epithelial mesotheliomas. Their antibody was only useful on frozen section tissue and showed immunostaining of 40 of 40 (100%) epithelial mesotheliomas. Nineteen well and moderately differentiated primary pulmonary adenocarcinomas failed to stain with the MEl antibody, but one poorly differentiated pulmonary adenocarcinoma showed intense immunostaining. 

Ordonez evaluated 31 epithelioid mesotheliomas and 29 pulmonary adenocarcinomas for E-cadherin and N-cadherin expression. They used the 5H9, HECD-1, and clone 36 anti-E-cadherin antibodies and the 3B9 and clone 32 anti-N-cadherin antibodies.Sixty-eight percent, 52%, and 19% of the epithelial mesotheliomas reacted with anti-E-cadherin clone 36, clone HECD-1, and 5H9, respectively. Seventy-four percent and 71% of epithelial mesotheliomas reacted with anti-N-cadherin clone 3B9 and clone 32, respectively. Ninety-three percent, 90%, and 90% of pulmonary adenocarcinomas reacted with anti-E-cadherin clone 36, clone HECD-1, and clone 5H9, respectively. Forty-five percent and 34% of pulmonary adenocarcinomas reacted with anti-N-cadherin clone 32 and clone 3B9, respectively. Ordonez concluded that the 5H9 anti-E-cadherin antibody had some utility in discriminating between pleural epithelioid mesothelioma and pulmonary adenocarcinoma. 

D2-40, a clone of podoplanin, is a recently developed commercially available antibody directed against the M2A antigen, a 40,000-kD sialoglycoprotein associated with germ cells and lymphatic endothelium. Chu and colleagues evaluated 53 cases of mesothelioma, 28 cases of reactive pleural tissue, 30 cases of pulmonary adenocarcinoma, 35 cases of renal cell carcinoma, 26 cases of ovarian serous carcinoma, 16 cases of invasive breast carcinoma, 11 cases of prostatic adenocarcinoma, and 7 cases of urothelial carcinoma. The authors found D2-40 expression in 51 of 53 (96%) mesotheliomas, 27 of 28 (96%) reactive pleural tissues, and 17 of 26 (65%) ovarian serous carcinomas. They did not find D2-40 in the other tumors examined. The authors also observed that the neoplastic cells immunostained in a cell membrane distribution. 

Concerning mesothelial-related antigens, 28 of 57 (49.1%) epithelial mesotheliomas immunostained for thrombomodulin compared to 13 of 211 (6.1%) adenocarcinomas, of which 7 were pulmonary adenocarcinomas. HBME-1 immunoreactivity was observed in 45 of 57 (78.9%) epithelial mesotheliomas, usually in a circumferentially thick or moderately thick distribution. 

These authors use a battery of antibodies to evaluate mesothelial proliferative lesions, including reactive and neoplastic processes. Keratin antibodies, with the exception of CK5/6, are generally not used to differentiate an epithelial mesothelioma from another neoplasm or from a reactive process, but are used to identify the extent of a neoplastic or reactive mesothelial cell process. The antibodies we use to differentiate a well or moderately well differentiated epithelial mesothelioma from a pulmonary adenocarcinoma or nonpulmonary adenocarcinoma include AE1/AE3 cytokeratin, CK5/6, CK7, CK20, vimentin, EMA, EIBME-1, calretinin, mesothe-lin, WTl, D2-40, caldesmon, CEA, LeuMl, B72.3, BerEP4, and TTE-1. 

The immunohistogram of a well to moderately well differentiated epithelial mesothelioma is shown in Fig. 12.51. A comparison of the immunohistochemical profile of well to moderately well differentiated epithelial mesothelioma and pulmonary adenocarcinoma is shown in Table 12.29. 

TABLE 12.29 Comparison of Immunohistochemical Profiles of Well to Moderately Well Differentiated Epithelial Mesotheliomas and Well to Moderately Well Differentiated Pulmonary Adenocarcinomas ... 

Several articles have been published discussing immunohistochemical tests used in distinguishing epithelial mesotheliomas from pulmonary adenocarcinomas and other carcinomas.These have been extensively reviewed by Ordonez. The most recent review by Ordonez evaluated 60 unequivocal epithelial mesotheliomas and 50 lung adenocarcinomas with a... 

TABLE 12.35 Antibodies Used to Distinguish Epithelial Mesothelioma from Pulmonary Adenocarcinoma and Other Carcinomas ... 

Unusual/uncommon types of mesothelioma should be mentioned because they can cause diagnostic confusion. Mucin-positive epithelial mesotheliomas are not uncommon." Between 1% and 5% of all moderately well to well differentiated epithelial mesotheliomas show mucicarmine and/or PAS-diastase staining (Fig. 12.59). Patterns of mucin staining have been extensively described by this author." Mucin-positive epithelial mesotheliomas most frequently express immunohistochemical markers that are negative in most epithelial mesotheliomas and usually positive in pulmonary adenocarcinomas (CEA, LeuMl, B72.3, BerEP4). Mucinpositive epithelial mesotheliomas express calretinin and... 

TABLE 12.36 Immunohistochemical Results of Epithelial Mesotheliomas and Pulmonary Adenocarcinomas ... 

Epithelial Mesotheliomas Grade of reactivity Pulmonary Adenocarcinomas Grade of reactivity ... 

Epithelial Mesothelioma Primary Pulmonary Adenocarcinoma Conclusion of Study ... 

Mullink H, Henzen-Logmans SC, Alons-van Kordelaan JJM, et al. Simultaneous immtmoenzyme staining of vimentin and cytokeratins with monoclonal antibodies as an aid in the differential diagnosis of malignant mesothelioma from pulmonary adenocarcinoma. Virch Arch B Pathol Anat. 1986 42 55-65. 

O Hara CJ, Corson JM, Pinkus GS, et al. MEl A monoclonal antibody that distinguishes epithelial-type mesothelioma from pulmonary adenocarcinoma and extra-pulmonary malignancies. Am J Pathol. 1990 136 421-428. 

Brown RW, Clark GM, Tandon AK, et al. Multiple-marker immunohistochemical phenotypes distinguishing malignant pleural mesothelioma from pulmonary adenocarcinoma. Hum Pathol. 1993 24 347-354. 

Sheibani K, Battifora H, Burke J. Antigenic phenotype of malignant mesotheliomas and pulmonary adenocarcinomas An immunohistologic analysis demonstrating the value of Leu-Ml antigen. Am Pathol. 1986 123 212-219. 

Otis CN, Carter O, Cole S, et al. Immunohistochemical evaluation of pleural mesothelioma and pulmonary adenocarcinoma. Am J Surg Pathol. 1987 11 445-456. 

Kawai T, Suzuki M, Torikata C, et al. Expression of blood group-related antigens and Helix pomatia agglutinin in malignant pleural mesothelioma and pulmonary adenocarcinoma. Hum Pathol. 1991 22 118-124. 

GominGE,NovelliL,BoddiV,etal.Galretinin, thrombomodulin, GEA and GDI5 A useful combination of immunohistochemical markers for differentiating pleural epithelial mesothelioma from peripheral pulmonary adenocarcinoma. Hum Pathol. 2001 32 529-536. 

Hammar SP, Bockus DE, Remington FL, et al. Mucin-positive epithelial mesotheliomas A histochemical, immrmohistochemi-cal and ultrastructural comparison with mucin-producing pulmonary adenocarcinomas. Ultra Pathol. 1996 20 293-325. 

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